Intra-ductal glutamine administration reduces oxidative injury during human pancreatic islet isolation
Intra-ductal glutamine administration reduces oxidative injury during human pancreatic islet isolation
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DOI：
10.1111/j.1600-6143.2005.01109.x
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发表时间：
2005-12-01
影响因子：
8.8
通讯作者：
Oberholzer, J
中科院分区：
文献类型：
--
作者：
Avila, J;Barbaro, B;Oberholzer, J
胰岛分离过程中的氧化应激诱导了一系列损伤胰岛和阻碍胰岛植入的事件。本研究评价了导管内谷氨酰胺给药后胰岛分离和移植的结果。通过主胰管用5 mM L-谷氨酰胺溶液（n = 6）或单独的胶原酶（n = 6）处理被认为不适合胰腺或胰岛移植的人胰腺。胰岛产量、活力、体外功能;评估氧化应激标志物[丙二醛（MDA）和谷胱甘肽（GSH）]和细胞凋亡。与对照组相比，谷氨酰胺组的胰岛产量显著增加（318，559 +/- 25，800对165，582 +/- 39，944平均值+/- SEM，p < 0.01）。谷氨酰胺组每个胰岛的凋亡细胞数量小于对照组。用谷氨酰胺处理的胰岛使血糖正常的裸鼠的百分比高于对照组（83%n = 10/12 vs.26%n = 6/23; p < 0.01），并且谷氨酰胺组达到血糖正常的时间缩短（1.83 +/-0.4 vs. 7. 3 +/-3天; p < 0.01）。谷氨酰胺给药增加了GSH水平（7.6 +/- 1.7 nmol/mg蛋白质vs.4.03 +/- 0.5 in control，p < 0.05）并减少了脂质过氧化（MDA 2.45 +/- 0.7 nmol/mg蛋白质vs.6.54 +/- 1.7 in control; p < 0.05）。我们的结论是，导管内注射谷氨酰胺可以减少氧化损伤和细胞凋亡，提高胰岛产量和移植后胰岛移植物的功能。
Oxidative stress during islet isolation induces a cascade of events injuring islets and hampering islet engraftment. This study evaluated islet isolation and transplantation outcomes after intra-ductal glutamine administration. Human pancreata deemed unsuitable for pancreas or islet transplantation were treated with either a 5 mM solution of L-glutamine (n = 6) or collagenase enzyme alone (n = 6) through the main pancreatic duct. Islet yield, viability, in vitro function; markers of oxidative stress [malondialdehyde (MDA) and Glutathione (GSH)] and apoptosis were assessed. Islet yields were significantly increased in the glutamine group compared to controls (318, 559 +/- 25, 800 vs. 165, 582 +/- 39, 944 mean +/- SEM, p < 0.01). The amount of apoptotic cells per islet was smaller in the glutamine group than the control. The percentage of nude mice rendered normoglycemic with glutamine-treated islets was higher than the controls (83% n = 10/12 vs. 26% n = 6/23; p < 0.01), and the time to reach normoglycemia was decreased in the glutamine group (1.83 +/- 0.4 vs. 7.3 +/- 3 days; p < 0.01). Glutamine administration increased GSH levels (7.6 +/- 1.7 nmol/mg protein vs. 4.03 +/- 0.5 in control, p < 0.05) and reduced lipid-peroxidation (MDA 2.45 +/- 0.7 nmol/mg of protein vs. 6.54 +/- 1.7 in control; p < 0.05). We conclude that intra-ductal administration of glutamine reduces oxidative injury and apoptosis and improves islet yield and islet graft function after transplantation.